Metabolism and Genetics

Group Leader

Paula Leandro

PhD (2001) in Pharmacy (Biochemistry), Universidade de Lisboa
Assistant Professor, Biochemistry and Human Biology, Faculdade de Farmácia, Universidade de Lisboa

The Research

Metabolism and Genetics 1Research at the Met&Gen group focus on the study of altered metabolic states in human diseases, in particular non-endoplasmic reticulum (ER)-associated rare inherited metabolic disorders (IMD) and some common diseases such as diabetes, obesity, cardiovascular disease (CVD), cancer and liver disease. The group uses molecular genetic approaches, biochemical and biophysical characterization of enzymes, transporters and channels involved in metabolic pathways, and cellular metabolic profiling by targeted mass spectrometry metabolomics to identify mechanisms of disease pathogenesis. This helps us to identify potential biomarkers, drug targets and drug candidates, with the final goal to translate our discoveries into clinical practice. The research evolved in 5 areas: 1) Genetic basis of non-ER IMDs; 2) Functional/structural characterization of non-ER-associated recombinant proteins (wild-type and variants); 3) Membrane channels and transporters as targets for drugs; 4) Protein-metabolome networks of drug-induced effects in liver/brain pathogenesis and; 5) Disturbed homocysteine metabolism, endothelial dysfunction and CVD.


Metabolism and Genetics 2

Ongoing Projects

Source: Sociedade Portuguesa de Doenças Metabólicas (SPDM)
Title: Next-generation sequencing for the molecular characterization of pyruvate dehydrogenase complex deficiency due to primary and secondary causes.
PI: Isabel Rivera
Period: 2017-2019

Source: Sociedade Portuguesa de Doenças Metabólicas (SPDM)
Title: New approaches for the treatment of Phenylketonuria: Evaluation of human phenylalanine hydroxylase (hPAH) formulations in cellular models.
PI: Paula Leandro
Period: 2016-2018

Source: EU-COST Action BM1406
Title: Ion channels and immune response toward a global understanding of immune cell physiology and for new therapeutic approaches IONCHAN-IMMUNRESPON
PI: Graça Soveral (management committee)
Period: 2015-2018

Source: PTDC/BIMMEC/ 0895/2014
New Drugs to Treat Non-alcoholic Fatty Liver and Progression to Cancer
PI: Cecília M. P. Rodrigues (Cell Fun Group, iMed.ULisboa); Participant: Margarida F. B. Silva
Period: 2016-2019

Source: Sociedade Portuguesa de Doenças Metabólicas (SPDM)
CYP46A1 as a New Therapeutic Target in Niemann-Pick Type C Disease
PI: Elsa Rodrigues (Cell Fun Group, iMed.ULisboa); Participant: Margarida F. B. Silva
Period: 2018-2019



Recent Most Relevant Publications

Barroso M, Kao D, Blom HJ, de Almeida IT, Castro R, Loscalzo J, Handy DE. S-adenosylhomocysteine induces inflammation through NFkB: A possible role for EZH2 in endothelial cell activation. Biochim Biophys Acta (Mol Basis Dis) 2016; 1862: 82-92.

de Almeida A, Mósca AF, Wragg D, Wenzel M, Kavanagh P, Barone G, Leoni S, Soveral G, Casini A. The mechanism of aquaporin inhibition by gold compounds elucidated by biophysical and computational methods. Chem Commun (Camb) 2017; 53: 3830-3833.

Leandro J, Saraste J, Leandro P, Flatmark T. PKU mutation p.G46S prevents the stereospecific binding of L-phenylalanine to the dimer of human phenylalanine hydroxylase regulatory domain. FEBS Open Bio 2017; 7: 195-203.

Moedas MF, Adam AAA, Farelo MA, IJlst L, Chamuleau RAFM, Hoekstra R, Wanders RJA, Silva MFB. Advances in methods for characterization of hepatic urea cycle enzymatic activity in HepaRG cells using UPLC-MS/MS. Anal Biochem 2017; 535: 47-55.

Pinheiro A, Silva MJ, Florindo C, Pavlu-Pereira H, Barroso M, Marques B, Correia H, Oliveira A, Gaspar A, Tavares de Almeida I, Rivera I. Complex genetic findings in a female patient with pyruvate dehydrogenase complex deficiency: null mutations in PDHX gene associated with unusual expression of the testis-specific PDHA2 gene in her somatic cells. Gene 2016; 591: 417-424.